Effect of eligibility burden on survival time in pancreatic cancer clinical trials.

Abstract

e23023 Background: Pancreatic ductal adenocarcinoma (PDAC) has median survival measured in months, yet the survival time cost of trial eligibility remains unquantified. We examined whether cumulative eligibility burden consumes a clinically meaningful share of expected remaining survival in PDAC and may thereby bias enrollment away from patients reflective of the real-world population. Methods: We identified 298 U.S. interventional PDAC trials that were recruiting or active but not recruiting. Eligibility criteria were extracted from ClinicalTrials.gov using a predefined rule-based search and manually validated on a random subset. Criteria were scored using a predefined Eligibility Time-Burden Score (ETBS, 0–4), a pragmatic, non-causal summary measure designed to capture time-critical eligibility barriers, with one point assigned for each of the following: ECOG ≤1 restriction, washout ≥21 days, mandatory tissue or biopsy, and major comorbidity exclusions. ETBS distributions were examined by trial phase, start year, and sponsor type. Population-level survival benchmarks were derived from SEER year-of-diagnosis 2018–2021 1-year relative survival to contextualize eligibility delays relative to expected remaining survival in newly diagnosed PDAC. Results: For many patients, a ≥28-day washout alone represents approximately 10% of expected remaining survival based on SEER benchmarks. Overall eligibility burden was substantial (mean ETBS 2.31). ECOG criteria were specified in 86.6% of trials, with 59.4% restricting enrollment to ECOG ≤1. Washout ≥21 days occurred in 69.1%, including ≥28 days in 63.4%. Mandatory tissue or biopsy was required in 28.9%, and 73.8% of trials excluded patients with major comorbidities. ETBS ≥2 occurred in 75.5% of trials, ETBS ≥3 in 48.7%, and the maximum ETBS (4) in 16.1%. Eligibility burden persisted beyond early-phase development, including Phase II trials (mean ETBS 2.27; ETBS ≥3 51.5%), with similar patterns across sponsor types. Conclusions: Protocol-defined eligibility criteria in contemporary pancreatic cancer trials represent a substantial time burden relative to patients’ expected remaining survival, with implications for trial feasibility and generalizability. These burdens persist beyond early-phase trials. Strict performance status thresholds, prolonged washouts, mandatory tissue collection, and broad comorbidity exclusions preferentially limit eligibility for patients who are older, have multimorbidity, or experience early functional decline. Eligibility burden reflects modifiable trial design choices and represents an actionable opportunity to align trial eligibility with the survival urgency of the PDAC population.